Nivolumab plus chemoradiotherapy in locally-advanced cervical cancer: the NICOL phase 1 trial.

Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial (NCT03298893) is designed to determine the safety/tolerance profile and the recommended phase-II dose of nivolumab with and following concurrent CRT in 16 women with locally advanced cervical cancer. Secondary endpoints include objective response rate (ORR), progression free survival (PFS), disease free survival, and immune correlates of response. Three patients experience grade 3 dose-limiting toxicities. The pre-specified endpoints are met, and overall response rate is 93.8% [95%CI: 69.8-99.8%] with a 2-year PFS of 75% [95% CI: 56.5-99.5%]. Compared to patients with progressive disease (PD), progression-free (PF) subjects show a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3+ T cells to PD-L1+ tumor cells and of FOXP3+ T cells to proliferating CD11c+ myeloid cells. PF show higher baseline levels of PD-1 and ICOS-L on tumor-infiltrating EMRA CD4+ T cells and tumor-associated macrophages, respectively; PD instead, display enhanced PD-L1 expression on TAMs, higher peripheral frequencies of proliferating Tregs at baseline and higher PD-1 levels at week 6 post-treatment initiation on CD4 and CD8 T cell subsets. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of locally advanced cervical cancer displaying pre-existing, adaptive immune activation is warranted.

Prophylactic Radical Fimbriectomy with Delayed Oophorectomy in Women with a High Risk of Developing an Ovarian Carcinoma: Results of a Prospective National Pilot Study.

Risk-reducing salpingo-oophorectomy is the gold standard for the prophylaxis of ovarian cancer in high-risk women. Due to significant adverse effects, 20-30% of women delay or refuse early oophorectomy. This prospective pilot study (NCT01608074) aimed to assess the efficacy of radical fimbriectomy followed by a delayed oophorectomy in preventing ovarian and pelvic invasive cancer (the primary endpoint) and to evaluate the safety of both procedures. The key eligibility criteria were pre-menopausal women ≥35 years with a high risk of ovarian cancer who refused a risk-reducing salpingo-oophorectomy. All the surgical specimens were subjected to the SEE-FIM protocol. From January 2012 to October 2014, 121 patients underwent RF, with 51 in an ambulatory setting. Occult neoplasia was found in two cases, with one tubal high-grade serous ovarian carcinoma. Two patients experienced grade 1 intraoperative complications. No early or delayed grade ≥3 post-operative complications occurred. After 7.3 years of median follow-up, no cases of pelvic invasive cancer have been noted. Three of the fifty-two patients developed de novo breast cancer. One BRCA1-mutated woman delivered twins safely. Twenty-five patients underwent menopause, including fifteen who had received chemotherapy for breast cancer, and twenty-three underwent menopause before the delayed oophorectomy, while two did not undergo a delayed oophorectomy at all. Overall, 46 women underwent a delayed oophorectomy. No abnormalities were found in any delayed oophorectomy specimens. Radical fimbriectomy followed by delayed oophorectomy appears to be a safe and well-tolerated risk-reducing approach, which avoids early menopause for patients with a high risk of breast and ovarian cancer.

Sentinel Lymph Node Biopsy in Uterine Cancer: Time for a Modern Approach.

Since the validation of the sentinel node technique (SLN) for vulvar cancer 20 years ago, this technique has been introduced in the management of operable cervical cancer and endometrial cancer. For cervical cancer a "one fits all" attitude has mainly been presented. However, this approach, consisting of a frozen section during the operation, can be discussed in some stages. We present and discuss the main option for each stage, as well as some secondary possibilities. For endometrial cancer, SLN is now the technique of choice for the nodal staging of low- and intermediate-risk groups. Some discussion exists for the high-risk group. We also discuss the impacts of using preoperatively the molecular classification of endometrial cancer. Patients with POLE or TP53 mutations could have different nodal staging. The story of SLN in uterine cancers is not finished. We propose a comprehensive algorithm of SLN in early cervical and endometrial cancers. However, several ongoing trials will give us important data in the coming years. They could substantially change these propositions.

Impact of the Area of Residence of Ovarian Cancer Patients on Overall Survival.

Survival disparities persist in ovarian cancer and may be linked to the environments in which patients live. The main objective of this study was to analyze the global impact of the area of residence of ovarian cancer patients on overall survival. The data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We included all the patients with epithelial ovarian cancers diagnosed between 2010 and 2016. The areas of residence were analyzed by the hierarchical clustering of the principal components to group similar counties. A multivariable Cox proportional hazards model was then fitted to evaluate the independent effect of each predictor on overall survival. We included a total of 16,806 patients. The clustering algorithm assigned the 607 counties to four clusters, with cluster 1 being the most disadvantaged and cluster 4 having the highest socioeconomic status and best access to care. The area of residence cluster remained a statistically significant independent predictor of overall survival in the multivariable analysis. The patients living in cluster 1 had a risk of death more than 25% higher than that of the patients living in cluster 4. This study highlights the importance of considering the sociodemographic factors within the patient's area of residence when developing a care plan and follow-up.

[How to improve the surgical trials quality in daily practice]. / Comment améliorer la qualité méthodologique et l'adoption en routine des résultats des essais chirurgicaux ?

Surgical studies have specific issues, such as quality assurance on procedures, standardization of techniques, surgeon effect, timing of randomization, blinding respect or choice of the reference arm. All these difficulties conducted to criticism many trials, and lack of results implementation. Indeed, adherence to methodological guidelines is often poor. Twelve recommendations were recently issued by the JAMA surgery revue for good practice in surgical studies to improve the quality of surgical trials in general and surgical oncology. We detail here the main issues of surgical trials in gynaecological oncology surgery, as well as possibilities of improvement for future studies.

Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Breast Magnetic Resonance Image Analysis for Surgeons Using Virtual Reality: A Comparative Study.

PURPOSE: The treatment of breast cancer, the leading cause of cancer and cancer mortality among women worldwide, is mainly on the basis of surgery. In this study, we describe the use of a medical image visualization tool on the basis of virtual reality (VR), entitled DIVA, in the context of breast cancer tumor localization among surgeons. The aim of this study was to evaluate the speed and accuracy of surgeons using DIVA for medical image analysis of breast magnetic resonance image (MRI) scans relative to standard image slice-based visualization tools. MATERIALS AND METHODS: In our study, residents and practicing surgeons used two breast MRI reading modalities: the common slice-based radiology interface and the DIVA system in its VR mode. Metrics measured were compared in relation to postoperative anatomical-pathologic reports. RESULTS: Eighteen breast surgeons from the Institut Curie performed all the analysis presented. The MRI analysis time was significantly lower with the DIVA system than with the slice-based visualization for residents, practitioners, and subsequently the entire group (P < .001). The accuracy of determination of which breast contained the lesion significantly increased with DIVA for residents (P = .003) and practitioners (P = .04). There was little difference between the DIVA and slice-based visualization for the determination of the number of lesions. The accuracy of quadrant determination was significantly improved by DIVA for practicing surgeons (P = .01) but not significantly for residents (P = .49). CONCLUSION: This study indicates that the VR visualization of medical images systematically improves surgeons' analysis of preoperative breast MRI scans across several different metrics irrespective of surgeon seniority.

Factors Associated With the Discussion of Fertility Preservation in a Cohort of 1,357 Young Breast Cancer Patients Receiving Chemotherapy.

PURPOSE: Female breast cancer (BC) patients exposed to gonadotoxic chemotherapy are at risk of future infertility. There is evidence of disparities in the discussion of fertility preservation for these patients. The aim of the study was to identify factors influencing the discussion of fertility preservation (FP). MATERIAL AND METHODS: We analyzed consecutive BC patients treated by chemotherapy at Institut Curie from 2011-2017 and aged 18-43 years at BC diagnosis. The discussion of FP was classified in a binary manner (discussion/no discussion), based on mentions present in the patient's electronic health record (EHR) before the initiation of chemotherapy. The associations between FP discussion and the characteristics of patients/tumors and healthcare practitioners were investigated by logistic regression analysis. RESULTS: The median age of the 1357 patients included in the cohort was 38.7 years, and median tumor size was 30.3 mm. The distribution of BC subtypes was as follows: 702 luminal BCs (58%), 241 triple-negative breast cancers (TNBCs) (20%), 193 HER2+/HR+ (16%) and 81 HER2+/HR- (6%). All patients received chemotherapy in a neoadjuvant (n=611, 45%) or adjuvant (n= 744, 55%) setting. A discussion of FP was mentioned for 447 patients (33%). Earlier age at diagnosis (discussion: 34.4 years versus no discussion: 40.5 years), nulliparity (discussion: 62% versus no discussion: 38%), and year of BC diagnosis were the patient characteristics significantly associated with the mention of FP discussion. Surgeons and female physicians were the most likely to mention FP during the consultation before the initiation of chemotherapy (discussion: 22% and 21%, respectively). The likelihood of FP discussion increased significantly over time, from 15% in 2011 to 45% in 2017. After multivariate analysis, FP discussion was significantly associated with younger age, number of children before BC diagnosis, physicians' gender and physicians' specialty. CONCLUSION: FP discussion rates are low and are influenced by patient and physician characteristics. There is therefore room for improvement in the promotion and systematization of FP discussion.

Laparoscopic management of advanced epithelial ovarian cancer after neoadjuvant chemotherapy: a phase II prospective multicenter non-randomized trial (the CILOVE study).

OBJECTIVE: The aim of this study was to explore the feasibility and safety of the laparoscopic approach after neoadjuvant chemotherapy among selected chemosensitive patients with advanced ovarian cancer. METHODS: The CILOVE study was a phase II prospective non-randomized multicenter study. It aimed to enroll 47 women with unresectable disease at the time of initial diagnosis (International Federation of Gynecology and Obstetrics (FIGO) stage IV and/or diffuse extensive carcinomatosis for advanced FIGO stage IIIC or patients unfit to withstand radical primary surgery), in response to chemotherapy and fit to undergo laparoscopy. RESULTS: Among the 48 patients enrolled in the trial, 44 (92%) patients underwent exploratory staging laparoscopy and, as a result, 41 patients were eligible for cytoreductive surgery. Among them, 32 were intended to be managed by laparoscopy and nine patients were managed by laparotomy. The conversion rate to laparotomy was 9.4% (3/32) and the reasons were multiple surgical adhesions (n=1), miliary carcinomatosis and adhesion to the intraperitoneal mesh (n=1), and poor laparoscopic evaluation of transverse colon involvement (n=1). All except one patient had optimal cytoreduction (97% complete cytoreduction, 3% incomplete cytoreduction (residual tumor <2.5 mm)). The median operative time was 267 min (range 146-415) and the median estimated blood loss was 150 mL (range 0-500). Two patients had intra-operative complications: one diaphragm rupture that was repaired during laparoscopy and one bradycardia. Six patients experienced early post-operative complications (<1 month), but there were no grade 3 and 4 complications (3 infections, 1 lymphoedema, 2 hemorrhage). After cytoreductive laparoscopy, the percentage of patients without progression at 12 months was 87.5%. CONCLUSIONS: Interval ovarian cytoreduction by a laparoscopic approach is safe and feasible for patients with a favorable response to chemotherapy. With the widespread use of neoadjuvant chemotherapy in the management of advanced ovarian cancer, a minimally invasive approach may be a potential option.

Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer.

PURPOSE: Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemoradiation or to predict relapse during the follow-up period. EXPERIMENTAL DESIGN: We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV E7 gene as a marker for residual disease compared to HPV integration site and PIK3CA mutations. Finally, the prognostic impact of circulating HPV E7 gene was assessed with its prediction value of relapse. RESULTS: HPV E7 gene was the most sensitive tumor marker, superior to both HPV integration sites and PIK3CA mutations in serum. Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (P = 0.02) and para-aortic lymph node involvement (P = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R = 0.39, P < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (P < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2-15) from HPV ctDNA detection. CONCLUSIONS: HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.See related commentary by Wentzensen and Clarke, p. 5733.

Breast Cancer (BC) Is a Window of Opportunity for Smoking Cessation: Results of a Retrospective Analysis of 1234 BC Survivors in Follow-Up Consultation.

Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer deaths in women. Smoking is the principal modifiable risk factor for cancers and has a negative influence on long-term survival. We conducted a retrospective study on consecutive BC survivors seen at follow-up consultations between 3 June and 30 October 2019 at Institut Curie, Paris, France. Smoking behaviors were evaluated prospectively via interviewer-administered questionnaires. The aim of this study was to describe smoking-related patient care at diagnosis and smoking cessation patterns in women with a history of BC. A total of 1234 patients were included in the study. Smoking status at diagnosis was missing from electronic health records in 32% of cases, including 13% of patients who smoke. Only 20% of the 197 patients currently smoking at diagnosis recalled having a discussion about smoking with a healthcare professional. Radiotherapists and surgeons were more likely to talk about complications than other practitioners. The main type of information provided was general advice to stop smoking (n = 110), followed by treatment complications (n = 48), while only five patients were referred to tobaccologists. Since diagnosis, 33% (n = 65) of the patients currently smoking had quit. Patients who quit had a lower alcohol consumption, but no other factor was associated with smoking cessation. The main motivation for tobacco withdrawal was the fear of BC relapse (63%). This study highlights room for improvement in the assessment of smoking behavior. Our data raise important perspectives for considering BC treatment and follow-up as a window of opportunity for smoking cessation.

Sentinel lymph node biopsy and morbidity outcomes in early cervical cancer: Results of a multicentre randomised trial (SENTICOL-2).

INTRODUCTION: Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated. MATERIALS AND METHODS: In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point. RESULTS: A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm). CONCLUSION: SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.

Molecular features of untreated breast cancer and initial metastatic event inform clinical decision-making and predict outcome: long-term results of ESOPE, a single-arm prospective multicenter study.

BACKGROUND: Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor. Very few studies have evaluated the impact of metastatic subtyping during the initial metastatic event in a prospective study. The genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting the findings transferability to clinical use. METHODS: We developed a multicenter, single-arm, prospective clinical trial in order to address these issues. Between November 2010 and September 2013, 123 eligible patients were included. Patients at the first, untreated metastatic event were eligible. All matched primary tumors and metastatic samples were centrally reviewed for pathological typing. Targeted and whole-exome sequencing was applied to matched pairs of frozen tissue. A multivariate overall survival analysis was performed (median follow-up 64 months). RESULTS: Per central review in 84 patients (out of 130), we show that luminal A breast tumors are more prone to subtype switching. By combining targeted sequencing of a 91 gene panel (n = 67) and whole-exome sequencing (n = 30), a slight excess of mutations is observed in the metastases. Luminal A breast cancer has the most heterogeneous mutational profile and the highest number of mutational signatures, when comparing primary tumor and the matched metastatic tissue. Tumors with a subtype change have more mutations that are private. The metastasis-specific mutation load is significantly higher in late than in de novo metastases. The most frequently mutated genes were TP53 and PIK3CA. The most frequent metastasis-specific druggable genes were PIK3CA, PTEN, KDR, ALK, CDKN2A, NOTCH4, POLE, SETD2, SF3B1, and TSC2. Long-term outcome is driven by a combination of tumor load and metastasis biology. CONCLUSIONS: Profiling of the first, untreated, metastatic event of breast cancer reveals a profound heterogeneity mostly in luminal A tumors and in late metastases. Based on this profiling, we can derive information relevant to prognosis and therapeutic intervention, which support current guidelines recommending a biopsy at the first metastatic relapse. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov ( NCT01956552 ).

Genetic markers and phosphoprotein forms of beta-catenin pß-Cat552 and pß-Cat675 are prognostic biomarkers of cervical cancer.

BACKGROUND: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality world wide and constitutes the third most common malignancy in women. The RAIDs consortium (http://www.raids-fp7.eu/) conducted a prospective European study [BioRAIDs (NCT02428842)] with the objective to stratify CC patients for innovative treatments. A "metagene" of genomic markers in the PI3K pathway and epigenetic regulators had been previously associated with poor outcome [2]. METHODS: To detect new, more specific, targets for treatment of patients who resist standard chemo-radiation, a high-dimensional Cox model was applied to define dominant molecular variants, copy number variations, and reverse phase protein arrays (RPPA). FINDINGS: Survival analysis on 89 patients with all omics data available, suggested loss-of-function (LOF) or activating molecular alterations in nine genes to be candidate biomarkers for worse prognosis in patients treated by chemo-radiation while LOF of ATRX, MED13 as well as CASP8 were associated with better prognosis. When protein expression data by RPPA were factored in, the supposedly low molecular weight and nuclear form, of beta-catenin, phosphorylated in Ser552 (pß-Cat552), ranked highest for good prognosis, while pß-Cat675 was associated with worse prognosis. INTERPRETATION: These findings call for molecularly targeted treatments involving p53, Wnt pathway, PI3K pathway, and epigenetic regulator genes. Pß-Cat552 and pß-Cat675 may be useful biomarkers to predict outcome to chemo-radiation, which targets the DNA repair axis. FUNDING: European Union's Seventh Program for research, technological development and demonstration (agreement N°304,810), the Fondation ARC pour la recherche contre le cancer.

Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome.

BACKGROUND: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. METHODS: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. FINDINGS: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. INTERPRETATION: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.

HPV DNA integration site as proof of the origin of ovarian metastasis from endocervical adenocarcinoma: three case reports.

BACKGROUND: Most endocervical adenocarcinomas are human papillomavirus (HPV)-related cancers associated with p16 immunostaining. Ovarian metastasis from cervical cancer is a rare phenomenon, the mechanism of dissemination remains unclear. The diagnosis of metastasis may be difficult to establish when the ovarian neoplasm presents features consistent with primary tumor. Immunohistochemical expression of p16 in ovarian tumors can guide the diagnosis of metastasis from HPV-related cervical cancer, but p16 positivity is nonspecific. Identical HPV genotype in the paired endocervical and ovarian tumors is a better marker for cervical origin, which may also be confirmed by identical HPV integration site. CASE PRESENTATION: Two women presented with HPV18 cervical adenocarcinoma. No signs of disease were visible on MRI after treatment. After several years of follow-up, mucinous ovarian tumors were discovered in both patients. Molecular analyses showed that the ovarian lesions were HPV18-positive; indicating a primary cervical origin. A third woman was diagnosed with grade 1 ovarian endometrioid carcinoma with no peritoneal carcinomatosis. Final histological examination and HPV genotyping revealed HPV18-related in situ endometrioid adenocarcinoma in the endocervix and HPV18-related invasive endometrioid adenocarcinoma in the endometrium and both ovaries. Additional molecular analyses performed in two patients identified the same HPV integration sites in both the ovarian and cervical tumors, confirming that the ovarian mass was a metastasis from the cervical adenocarcinoma. CONCLUSION: We report three new cases of ovarian neoplasia in which the diagnosis of metastasis from cervical cancer was supported by the same HPV genotype and the same integration site in the paired cervical and ovarian tumors. To our knowledge, this is the first report of molecular evidence of the cervical origin of an ovarian metastasis. HPV screening should be performed in ovarian tumors for all patients with history of cervical neoplasia.

A New Transcutaneous Method for Breast Cancer Detection with Dogs.

We developed a new transcutaneous method for breast cancer detection with dogs: 2 dogs were trained to sniff skin secretion samples on compresses that had been worn overnight by women on their breast, and to recognize a breast cancer sample among 4 samples. During the test, the dogs recognized 90.3% of skin secretion breast cancer samples. This proof-of-concept study opens new avenues for the development of a reliable cancer diagnostic tool integrating olfactory abilities of dogs.

Diagnostic Performance of Ultrasound-Guided Fine-Needle Aspiration of Nonpalpable Breast Lesions in a Multidisciplinary Setting: The Institut Curie's Experience.

OBJECTIVES: To assess the diagnostic performance of ultrasound-guided fine-needle aspiration (USFNA) in nonpalpable breast lesions (NPBLs) in a multidisciplinary setting. METHODS: In total, 2,601 NPBLs underwent USFNA by a radiologist-pathologist team. Gold-standard diagnosis was based on surgery, core-needle biopsy, or 1-year imaging follow-up. USFNA's diagnostic performance was analyzed in different clinical and imaging subgroups. RESULTS: USFNA's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 92.6% (95% confidence interval [CI], 90.8%-94.2%), 96.8% (95% CI, 95.8%-97.6%), 94.8% (95% CI, 93.2%-96.1%), and 95.4% (95% CI, 94.3%-96.4%). The best PPV was achieved in Breast-Imaging Reporting and Data System (BI-RADS) categories 4C and 5 and the best NPV in BI-RADS categories 2, 3, and 4A and in patients younger than 50 years. The mitotic count, BI-RADS categories, associated palpable cancer, and age (<50 or ≥50 years) were statistically independent factors ( P < .05) between USFNA's false-negative and true-positive results. CONCLUSIONS: USFNA is a robust diagnostic procedure in NPBLs. Age and the BI-RADS category of the lesion are important factors determining its performance.